GSK3 is a negative regulator of the thermogenic program in brown adipocytes

Abstract Brown adipose tissue is a promising therapeutic target in metabolic disorders due to its ability to dissipate energy and improve systemic insulin sensitivity and glucose homeostasis. β-Adrenergic stimulation of brown adipocytes leads to an increase in oxygen consumption and induction of a t...

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Autores principales:	Lasse K. Markussen, Sally Winther, Barton Wicksteed, Jacob B. Hansen
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/64ae880b3c6846a18c688151f4e5eae9
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spelling	oai:doaj.org-article:64ae880b3c6846a18c688151f4e5eae92021-12-02T12:32:10ZGSK3 is a negative regulator of the thermogenic program in brown adipocytes10.1038/s41598-018-21795-y2045-2322https://doaj.org/article/64ae880b3c6846a18c688151f4e5eae92018-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-21795-yhttps://doaj.org/toc/2045-2322Abstract Brown adipose tissue is a promising therapeutic target in metabolic disorders due to its ability to dissipate energy and improve systemic insulin sensitivity and glucose homeostasis. β-Adrenergic stimulation of brown adipocytes leads to an increase in oxygen consumption and induction of a thermogenic gene program that includes uncoupling protein 1 (Ucp1) and fibroblast growth factor 21 (Fgf21). In kinase inhibitor screens, we have identified glycogen synthase kinase 3 (GSK3) as a negative regulator of basal and β-adrenergically stimulated Fgf21 expression in cultured brown adipocytes. In addition, inhibition of GSK3 also caused increased Ucp1 expression and oxygen consumption. β-Adrenergic stimulation triggered an inhibitory phosphorylation of GSK3 in a protein kinase A (PKA)-dependent manner. Mechanistically, inhibition of GSK3 activated the mitogen activated protein kinase (MAPK) kinase 3/6-p38 MAPK-activating transcription factor 2 signaling module. In summary, our data describe GSK3 as a novel negative regulator of β-adrenergic signaling in brown adipocytes.Lasse K. MarkussenSally WintherBarton WicksteedJacob B. HansenNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-12 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Lasse K. Markussen Sally Winther Barton Wicksteed Jacob B. Hansen GSK3 is a negative regulator of the thermogenic program in brown adipocytes
description	Abstract Brown adipose tissue is a promising therapeutic target in metabolic disorders due to its ability to dissipate energy and improve systemic insulin sensitivity and glucose homeostasis. β-Adrenergic stimulation of brown adipocytes leads to an increase in oxygen consumption and induction of a thermogenic gene program that includes uncoupling protein 1 (Ucp1) and fibroblast growth factor 21 (Fgf21). In kinase inhibitor screens, we have identified glycogen synthase kinase 3 (GSK3) as a negative regulator of basal and β-adrenergically stimulated Fgf21 expression in cultured brown adipocytes. In addition, inhibition of GSK3 also caused increased Ucp1 expression and oxygen consumption. β-Adrenergic stimulation triggered an inhibitory phosphorylation of GSK3 in a protein kinase A (PKA)-dependent manner. Mechanistically, inhibition of GSK3 activated the mitogen activated protein kinase (MAPK) kinase 3/6-p38 MAPK-activating transcription factor 2 signaling module. In summary, our data describe GSK3 as a novel negative regulator of β-adrenergic signaling in brown adipocytes.
format	article
author	Lasse K. Markussen Sally Winther Barton Wicksteed Jacob B. Hansen
author_facet	Lasse K. Markussen Sally Winther Barton Wicksteed Jacob B. Hansen
author_sort	Lasse K. Markussen
title	GSK3 is a negative regulator of the thermogenic program in brown adipocytes
title_short	GSK3 is a negative regulator of the thermogenic program in brown adipocytes
title_full	GSK3 is a negative regulator of the thermogenic program in brown adipocytes
title_fullStr	GSK3 is a negative regulator of the thermogenic program in brown adipocytes
title_full_unstemmed	GSK3 is a negative regulator of the thermogenic program in brown adipocytes
title_sort	gsk3 is a negative regulator of the thermogenic program in brown adipocytes
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/64ae880b3c6846a18c688151f4e5eae9
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GSK3 is a negative regulator of the thermogenic program in brown adipocytes

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